Immunodeficiency states, both cell mediated and humoral, may be a primary pathological manifestation or occur secondary to other diseases such as cancer. This project will investigate the role of suppressor cells in the pathogenesis of immunodeficiency states. We have demonstrated by co-cultivation techniques leukocyte subpopulations capable of suppressing B cell and/or T cell associated functions in the peripheral blood of immunodeficient patients and have correlated these observations with the clinical status of the patients under investigation. We propose to isolate suppressor cells from the patients described by selective rosetting techniques, column chromatography, adsorption on solid state matrices, density gradient and sedimentation velocity separations and the use of specific antisera. Studies by ourselves and others have already demonstrated the selective radiosensitivity of naturally occurring human suppressor cells. We shall further characterize these cells on the basis of surface marker properties. Particular attention will be directed to the newly described T cell subpopulations such as T gamma and T microns lymphocytes and their roles in immunoregulation. We are presently examining the immunoregulatory role of prostaglandins. Additional efforts will be directed at the biochemical isolation and characterization of other human soluble suppressor substances. Studies are presently underway in our laboratories using Marbrooke flasks to separate suppressor cells from normal donor cells by membrane filters, allowing only soluble factors to pass between the separated populations. Thus the characterization of a cellular and biochemical mechanism leading to immunodeficiency would be the first step in developing new therapeutic modalities for these conditions.